Growth hormone, insulin-like growth factors, and IGF binding proteins

Growth hormone and insulin-like growth factors are essential for longitudinal growth and maintenance of the mammalian skeleton. These recombinant proteins are used to treat short stature and other growth defects in children. Additionally, rhGH is now an established part of the treatment algorithm for pituitary insufficiency. But neither growth hormone nor IGF-I is approved for the treatment of osteoporosis. In part this is because the skeletal effects of growth hormone and IGF-I are complex, temporal, and cell specific. Their actions include stimulation of bone formation, recruitment of osteoblasts and osteoclasts, and targeted changes in the osteocyte. In addition, IGF-I is essential for the anabolic effect of parathyroid hormone on bone, and its signaling nodes interact with other major anabolic factors such as the Wnts and BMPs. IGF-I may also be important in regulating substrate metabolism, and in particular, glycolysis in osteoblasts. This review focuses on the systemic and local actions of growth hormone, insulin-like growth factors, and their binding proteins and proteases.